Department of General Practice, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Infectious Disease, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Front Immunol. 2023 Aug 23;14:1204338. doi: 10.3389/fimmu.2023.1204338. eCollection 2023.
Hepatocellular carcinoma (HCC) comprises several distinct molecular subtypes with varying prognostic implications. However, a comprehensive analysis of a prognostic signature for HCC based on molecular subtypes related to disulfidptosis and glycolysis, as well as associated metabolomics and the immune microenvironment, is yet to be fully explored.
Based on the differences in the expression of disulfide-related glycolytic genes (DRGGs), patients with HCC were divided into different subtypes by consensus clustering. Establish and verify a risk prognosis signature. Finally, the expression level of the key gene SLCO1B1 in the signature was evaluated using immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) in HCC. The association between this gene and immune cells was explored using multiplex immunofluorescence. The biological functions of the cell counting kit-8, wound healing, and colony formation assays were studied.
Different subtypes of patients have specific clinicopathological features, prognosis and immune microenvironment. We identified seven valuable genes and constructed a risk-prognosis signature. Analysis of the risk score revealed that compared to the high-risk group, the low-risk group had a better prognosis, higher immune scores, and more abundant immune-related pathways, consistent with the tumor subtypes. Furthermore, IHC and qRT-PCR analyses showed decreased expression of SLCO1B1 in HCC tissues. Functional experiments revealed that SLCO1B1 overexpression inhibited the proliferation, migration, and invasion of HCC cells.
We developed a prognostic signature that can assist clinicians in predicting the overall survival of patients with HCC and provides a reference value for targeted therapy.
肝细胞癌 (HCC) 包含几个不同的分子亚型,具有不同的预后意义。然而,基于与二硫键分解代谢和糖酵解相关的分子亚型、相关代谢组学和免疫微环境,对 HCC 的预后特征进行综合分析尚未得到充分探索。
根据二硫键相关糖酵解基因 (DRGG) 的表达差异,通过共识聚类将 HCC 患者分为不同亚型。建立并验证风险预后特征。最后,使用免疫组织化学 (IHC) 和实时定量 PCR (qRT-PCR) 评估特征中关键基因 SLCO1B1 在 HCC 中的表达水平。使用多重免疫荧光探索该基因与免疫细胞的关联。研究细胞计数试剂盒-8、划痕愈合和集落形成测定的生物学功能。
不同亚型的患者具有特定的临床病理特征、预后和免疫微环境。我们确定了七个有价值的基因并构建了一个风险预后特征。风险评分分析表明,与高风险组相比,低风险组的预后更好,免疫评分更高,免疫相关途径更丰富,与肿瘤亚型一致。此外,IHC 和 qRT-PCR 分析显示 HCC 组织中 SLCO1B1 的表达降低。功能实验表明,SLCO1B1 的过表达抑制了 HCC 细胞的增殖、迁移和侵袭。
我们开发了一个预后特征,可以帮助临床医生预测 HCC 患者的总生存期,并为靶向治疗提供参考价值。